Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gelatin microspheres containing recombinant human interferon alpha A/D (A/D-IFN) (IFN-microspheres) potentiated the antitumor activity of mouse peritoneal macrophages (M phi) much more efficiently than free A/D-IFN. M phi acquired the inhibitory activity on tumor cell growth by the ingestion of IFN-microspheres without the aid of lipopolysaccharide (LPS), though LPS was required as a second signal for activating M phi primed with free IFN. The IFN-microspheres were much more efficient than free IFN plus LPS in respect of the IFN amount and the time required for M phi activation. Furthermore, M phi pretreated with the IFN-microspheres maintained their activated state for a much longer period than those pretreated with free A/D-IFN plus LPS. A monoclonal anti-IFN-alpha A antibody, which was capable of neutralizing A/D-IFN, did not interfere with the M phi activation by the IFN-microspheres. Even human IFN-alpha A was effective in activating murine M phi similarly to A/D-IFN, when given in the form of IFN-microspheres, though human IFN-alpha A in the free form was ineffective. These results argue that the mechanism of M phi activation by the IFN-microspheres is different from that by free IFN.
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PMID:Potentiation of antitumor activity of macrophages by recombinant interferon alpha A/D contained in gelatin microspheres. 313 17

The ability of lipopolysaccharide to induce major histocompatibility complex hyperexpression in vivo in a variety of mouse tissues--particularly kidney--and the effect of cyclosporine on this process were studied. MHC expression was measured by a radiolabeled antibody-binding assay using tissue homogenates, as well as by assessment of tissue sections by indirect immunoperoxidase staining. LPS administered to mice in two doses, 4 days apart, induced an increase in class I expression in several tissues but also induced an increase in class II expression in kidney. A similar increase in class II expression in kidney was not elicited with polyinosinic acid/polycytidylic acid, an agent that induces release of IFN-alpha/beta and increases class I MHC product expression. Thus we reasoned that LPS in vivo may release IFN-gamma, which then induces increased expression of MHC products. We validated this hypothesis by demonstrating that monoclonal antibody against IFN-gamma inhibited the induction of renal MHC products by LPS. However, the LPS effects did not require the participation of T cells, being demonstrable in nude mice and in mice with severe combined immunodeficiency. Moreover, the effect of LPS on MHC expression in normal and nude mice was inhibited by in vivo administration of monoclonal antibody against IFN-gamma just as it was in normal mice. Thus the class II hyperexpression that follows LPS is apparently mediated by non T cells and is due to the systemic release of IFN-gamma. This mechanism was inhibited by high doses of CsA in vivo, both in normal and in nude mice. The results indicate that there is a non T cell pathway for IFN-gamma release (and MHC induction) in vivo that is sensitive to CsA. This observation raises the possibility that some of the immunosuppressive effects of CsA may be due to inhibition of mediator release from non T cells.
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PMID:Effects of cyclosporine on systemic MHC expression. Evidence that non-T cells produce interferon-gamma in vivo and are inhibitable by cyclosporine. 313 68

The combined effect of hydrocortisone (HC) and interferon-gamma and -alpha (IFN-gamma and -alpha) on human blood monocytes (Mo) interleukin 1 (IL 1) secretion was investigated. IL 1 was generated by treating the fresh or aged Mo with lipopolysaccharide (LPS), and quantitated by radioimmunoassay (RIA). Hydrocortisone, at the pharmacological attainable concentration of 10(-5) molar (M), markedly suppressed fresh Mo IL 1 secretion but had no effect at lower tested doses. Addition of IFN-gamma enhanced the IL 1 secretion of fresh Mo; however, the simultaneous addition of 10(-5) M HC and IFN-gamma resulted in marked suppression of the monokine release. Monocytes, when cultured in vitro for three days, lost the capacity to secrete IL 1. The loss of IL 1 secretory potential of aged Mo was prevented by preincubating them with IFN-gamma prior to LPS stimulation. IFN-alpha was ineffective in this regard. Aged Mo, pretreated with the combination of IFN-gamma and HC were still able to secrete abundant quantities of IL 1, demonstrating the failure of HC to suppress the IFN-gamma-induced augmentation of IL 1 secretory potential. Even suprapharmacologic doses of HC (10(-4) M) did not inhibit this enhancement and actually further augmented it. Thus, therapeutic concentrations of HC suppress IL 1 secretion of fresh Mo even in the presence of IFN-gamma; however, therapeutic or suprapharmacologic concentrations of HC do not inhibit the IL 1 secretory capacity of IFN-gamma-treated aged Mo.
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PMID:Failure of hydrocortisone to suppress the interferon-gamma-induced augmentation of interleukin 1 secretion of aged human monocytes. 313 48

The human myelomonocytic cell line RC2a expressed procoagulant activity following stimulation with human lymphokine (LK) prepared by stimulating peripheral blood mononuclear cells with either mitogens (Concanavalin A, phytohaemagglutinin or antigen (tuberculin). Induction was rapid, with optimal activity observed between 6 and 8 h, was decreased in cultures containing serum and was not inhibited by actinomycin D or cycloheximide. The LK activity was not inhibited by an anti-interferon gamma (IFN gamma) antibody. IFN gamma and phorbol myristate acetate (PMA) had no activity but acted in synergy to induce procoagulant expression; interferon alpha plus PMA were without effect. In contrast to the LK-induced response, procoagulant induced by IFN gamma/PMA was not detected for up to 8 h and steadily rose over 24-48 h culture and was dependent on new protein and RNA synthesis. Bacterial lipopolysaccharide, a potent inducer of thromboplastin on normal human monocytes, failed, either alone or in combination with LK, IFN gamma, PMA or IFN gamma plus PMA, to activate procoagulant expression on RC2a cells. Both LK and IFN gamma/PMA-induced procoagulant had properties of thromboplastin expressed both intracellularly and on intact, viable cells. This study shows that RC2a cells are responsive to factors produced as the result of an activated cell-mediated immune response which may therefore contribute to the coagulopathies common to this form of malignancy.
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PMID:Procoagulant induction by human lymphokine and interferon gamma/PMA on a myelomonocytic cell line, RC2a. 314 14

We investigated the role of interleukin 1 alpha (IL 1 alpha) in the pathogenesis of chronic liver disease. IL 1 alpha production by peripheral blood monocytes was measured with a specific, sensitive double-antibody radioimmunoassay. When monocytes were cultured for two days with bacterial lipopolysaccharide (LPS), IL 1 alpha production in asymptomatic hepatitis B virus carrier (ASC) and patients with chronic active hepatitis (CAH) was equivalent to that of controls (168 +/- 31 U/ml, mena +/- SD), while IL 1 alpha levels generated by monocytes from liver cirrhosis (LC) (117 +/- 45 U/ml, p less than 0.01) were significantly lower than controls. When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml. IL 1 alpha production in ASC did not differ from controls. On the other hand, IL 1 alpha production in patients with CAH (241 +/- 58 U/ml, p less than 0.05) and LC (189 +/- 70 U/ml, p less than 0.01) were significantly diminished in comparison with controls although there was considerable overlap. Serial study demonstrated that IL 1 alpha production rose significantly during acute deterioration of illness with marked rise in serum alanine aminotransferase. The addition of sera to normal monocytes cultures resulted in significantly enhanced suppression (p less than 0.05) for IL 1 alpha production in comparison with that of control sera. These findings indicate that decreased monocyte function and serum inhibitor(s) for IL 1 alpha production could contribute to the pathogenesis of chronic liver disease.
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PMID:Interleukin 1 alpha production by peripheral blood monocytes from patients with chronic liver disease and effect of sera on interleukin 1 alpha production. 314 31

The objective of these studies was to investigate mechanisms of regulation of interleukin 1 (IL-1) production by human monocytes. IL-1 production was measured by augmentation of phytohemagglutinin-induced proliferation of murine thymocytes. Adherent human monocytes incubated in medium for one day exhibited a marked decrease in lipopolysaccharide (LPS)-induced IL-1 production over a second day. Cells pre-incubated in 100 U/ml gamma interferon (gamma-IFN) for 24 h displayed a partial to complete maintenance of LPS-induced IL-1 production. Studies with inhibitors of cyclo-oxygenase or lipoxygenase indicated that prostaglandins or leukotrienes were not responsible for the alterations in IL-1 production observed with cultured cells or for the effects of gamma-IFN. Monocytes were pre-incubated in cycloheximide for 24 h and the drug was washed out. These cells exhibited an enhancement in IL-1 production over a second 24 h culture in the presence of 2 ng/ml LPS. Furthermore, the partial maintenance of LPS-induced IL-1 production seen after cells were pre-incubated in gamma-IFN was markedly increased by the inclusion of 0.25 microgram/ml cycloheximide during the 24 h pre-incubation. These results indicate that IL-1 production may be inhibited by newly-synthesized proteins during maturation in vitro or differentiation of monocytes into macrophages. Pre-incubation in gamma-IFN and cycloheximide leads to separate but synergistic effects on the maintenance of LPS-induced IL-1 production in cultured monocytes.
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PMID:Regulation of interleukin 1 production in human monocytes. I. Effects of gamma-interferon and cycloheximide. 314 77

Recently we presented evidence that cellular immune responses are associated with increased in-vitro and in-vivo excretion of neopterin (Huber et al., 1983) and that, in vitro at least, macrophages and IFN-gamma play a key role in the induction of this phenomenon (Huber et al., 1984). Although this marker is increasingly applied for monitoring of human disease, there is limited knowledge about the mechanism(s) responsible for its increased biosynthesis during inflammatory states. To further elucidate this question we evaluated neopterin and IFN-levels in culture supernatants of human blood cells and in patients' sera. Cells or patients were exposed to a panel of recombinant cytokines, alloantigens or lipopolysaccharide. To investigate indirect stimulation by induction of production of endogenous IFNs, the impact of neutralization of IFNs by addition of specific antibodies was also studied. The data confirm our previous results which identified the monocyte/macrophage as the main producer cell among human blood cells. They further demonstrate that, at least in vitro, IFN-gamma, IFN-alpha and LPS can all stimulate neopterin release independently from each other. Thirdly, they indicate that stimuli such as alloantigens or TNF-alpha can indirectly enhance neopterin release by their capacity to induce production of endogenous IFN-gamma. On the basis of these data we conclude that enhanced neopterin biosynthesis does not necessarily relate to activation of T cells but can also be caused by non-immune stimuli.
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PMID:In-vitro and in-vivo studies on the induction of neopterin biosynthesis by cytokines, alloantigens and lipopolysaccharide (LPS). 314 78

Recombinant murine gamma interferon (rMuIFN-gamma) was found to bind reversibly to a specific high-affinity surface receptor on L929 cells; neither murine alpha or beta nor human gamma IFN competed for receptor binding. Encapsulation of the rMuIFN-gamma in either negatively or positively charged liposomes reduced its immediate ability to bind to this surface receptor. Disruption of liposome integrity with detergent resulted in full ability of the rMuIFN-gamma to bind to the membrane receptor. Incubation of the liposomal IFN in serum-containing medium resulted in significant leakage so that the IFN was able to bind to its surface receptor. Assessment of the biological activity of the rMuIFN-gamma preparations revealed that full antiviral activity was observed in vitro with the liposomal IFN preparations without their prior disruption by detergent. The antiviral activity observed with either free or liposomal IFN was neutralized completely by antibodies against rMuIFN-gamma. Both free and liposomal rMuIFN-gamma, in conjunction with bacterial lipopolysaccharide, were also able to activate murine peritoneal macrophages to the tumoricidal state. Again, this activity of both free and liposomal IFN could be neutralized completely by antibody. These results indicate that although rMuIFN-gamma can be effectively incorporated into liposomes, it must ultimately leak out of the liposome in order to mediate its biological effects; these effects are triggered after the IFN binds to its cell surface receptors.
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PMID:Biological activity of liposome-encapsulated murine interferon gamma is mediated by a cell membrane receptor. 315 18

Murine peritoneal macrophages activated for cytotoxicity by trehalose dimycolate in vivo and lipopolysaccharide in vitro released cytostatic factor(s) against EMT6 target cells, in 8-hr conditioned medium (CM). The cytostatic factor(s) completely blocked DNA synthesis by EMT6 cells within 16 hr. Other cell lines are less sensitive (P815 and R-L929) or resistant (KB and HT29) to the cytostatic effect of CM. The anti-proliferative activity of CM had a MW greater than 10,000 Da, as judged by ultrafiltration. It was destroyed by proteases and strongly inhibited by P815 cell product(s). Conditioned media from nonactivated macrophages were not cytostatic against EMT6 cells. No relationship was found between cytostatic factor(s) in CM and interleukin 1 (IL-1), tumor necrosis factor alpha (TNF-alpha), and interferon-alpha/beta (IFN-alpha/beta): the growth of EMT6 cells was unaffected by Hu.r.IL-is and Hu.r.TNF-alpha and was only slightly inhibited by IFN-alpha/beta. Furthermore, cytostatic CM contained low levels of TNF and IFN activities. Finally, antibodies raised against murine IFN-alpha/beta had no effect on the cytostatic activity of CM.
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PMID:Cytostatic product(s) released by activated macrophages, unrelated to interleukin 1, tumor necrosis factor alpha, and interferon-alpha/beta. 326 36

The effect was investigated of combinations of cytokines known to be cytostatic for some tumor cells, namely interleukin 1 alpha (IL-1 alpha), interferon-beta (IFN-beta), and tumor necrosis factor (TNF), on the growth and differentiation of the mouse myeloid leukemic cell line, M1, cells. IL-1 alpha, IFN-beta, and TNF by themselves are antiproliferative for M1 cells. Treatment of cells with a mixture of any two of the three cytokines resulted in at least additive growth inhibition. None of these cytokines by themselves induced differentiation of M1 cells as assessed by increased expression of Fc receptors (FcR), stimulation of phagocytic activity and by morphologic criteria. However, as little as 1 U/ml IL-1 alpha in conjunction with IFN-beta or TNF increased FcR expression, phagocytic activity and morphologic changes in addition to inhibiting the growth of M1 cells. The combination of IFN-beta and TNF did not induce differentiation, although the growth of the cells was markedly inhibited. Both TNF and lipopolysaccharide (LPS) induced the in vitro production of IFN activity by M1 cells. Furthermore, the induction of differentiation of M1 cells by a combination of IL-1 alpha with either IFN-beta, TNF, or LPS was inhibited by antibody against mouse IFN-beta. Therefore, it appears that IFN-beta provides one of the two required signals for differentiation of M1 cells by these combinations of stimulants, the other being IL-1. Furthermore, the cytostatic effect of TNF by itself on M1 cells was also partly blocked by anti-IFN-beta antibody, suggesting that IFN-beta is also involved in the growth inhibitory effect of TNF for M1 cells. In contrast, the cytostatic effect of IL-1 on M1 cells was not blocked by anti-IFN-beta antibody. In conclusion, both the cytostatic and differentiative effect of TNF appear to be mediated by IFN-beta. Thus, the combination of IL-1 and IFN-beta or inducers of IFN-beta resulted in terminal differentiation of M1 cells. Northern blot analysis using cDNAs for murine IFN-beta1 or human IFN-beta2 showed an increased expression of mRNA for IFN-beta1 but not for IFN-beta2 by stimulation with TNF or LPS, strongly suggesting that IFN-beta 1 rather than IFN-beta 2 is responsible for TNF or LPS effects.
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PMID:Synergistic interactions of interleukin 1, interferon-beta, and tumor necrosis factor in terminally differentiating a mouse myeloid leukemic cell line (M1). Evidence that interferon-beta is an autocrine differentiating factor. 327 16


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